A convenient route to enantiomerically pure, conjugated dienes from sugar allyltin derivatives

Article abstract of DOI:10.1016/S0957-4166(00)00135-X

The transformation of sugar allyltin derivatives into enantiomerically pure dienes (R*-CH=CH-CH=CH₂) is presented. The internal double bond with the trans-configuration is formed regardless of the configuration of the starting sugar allyltin. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00135-X

Tetrahedron: Asymmetry 11 (2000) 1997±2006
A convenient route to enantiomerically pure, conjugated
dienes from sugar allyltin derivatives
S•awomir Jarosz,* Stanislaw Skora and Katarzyna Szewczyk
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw, Poland
Received 20 March 2000; accepted 3 April 2000
Abstract
The transformation of sugar allyltin derivatives into enantiomerically pure dienes (R*±CHˆCH±
CHˆCH2) is presented. The internal double bond with the trans-con®guration is formed regardless of the
con®guration of the starting sugar allyltin. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The Diels±Alder reaction is one of the most important processes in the creation of carbon±
carbon bonds.1 Application of chiral, enantiomerically pure dienes allows preparation of carbo-
cyclic compounds in enantiomerically pure form. Simple monosaccharides are convenient starting
materials for the preparation of such compounds, since most transformations of sugar molecules
can be performed with high regio- and stereoselectivity.
Many useful methods for the preparation of conjugated diene systems from sugars are reported
in the literature.2 Recently, we elaborated a convenient method for the synthesis of such mole-
culesÐdienoaldehydes 2Ðfrom sugar allyltins3 1 (Fig. 1).
Treatment of organometallic products 1 with a mild Lewis acid (e.g. zinc chloride) caused
their conversion into the trans-dienes3 2Ðuseful synthons in the stereoselective preparation of
enantiomerically pure bicyclo[4.3.0]nonene4 and bicyclo[4.4.0]decene5 derivatives (Fig. 1; 3 and 4,
respectively).
2. Results and discussion
The method of conversion of the allyltin derivatives into the diene system is based on a rear-
rangement±elimination procedure which requires the presence of an alkoxy function at the d
* Corresponding author. E-mail: sljar@icho.edu.pl
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00135-X

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S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
Figure 1. Synthesis of chiral dienes from allyltin pyranosides and their application in synthesis
position. We have observed that this process a€ords the trans-dienes exclusively, regardless of the
con®guration of starting allyltin derivative.6 Extension of this methodology for the preparation of
other types of sugar-derived dienes is presented.
2.1. Synthesis of the dienes substituted with the furanose ring
The preparation of chiral dienes substituted with a furanose ring consists of two steps: (i)
transformation of a simple monosaccharide into the allyltin derivative; and (ii) treatment of the
latter with a Lewis acid that should provide title compounds via a rearrangement±elimination
sequence. The methodology is outlined in Scheme 1.
Scheme 1. (i) (COCl)2, DMSO, Et3N; (ii) Ph3PˆCHCO2Me; (iii) DIBAL-H; (iv) (a) NaH, THF, 30 min; (b) CS2, 30
min; (c) MeI, 2 h; (v) toluene, re¯ux, 3 h; (vi) Bu3SnH, AIBN, 110ꢀC; (vii) ZnCl2, CH2Cl2, rt; (viii) Ph3PˆCHCHO; (ix)
Ph3PˆCH2

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1999
Thus, methyl 2,3,5-tri-O-benzyl-b-d-galactofuranoside7 (5) was converted into aldehyde 6 with
the Swern reagent and further to a,b-unsaturated estery 7 by reaction with carbomethoxy-
methylenetriphenylphosphorane (Ph3PˆCH±CO2Me). Reduction of the ester function with
DIBAL-H gave allylic alcohol 8, which was transformed into xanthate 9 by standard methodology.
Thermal [3,3] rearrangement of the latter a€orded thiocarbonate 10, which, upon reaction with
tributyltin hydride, gave the desired organometallic product 11 as a single trans-isomer.
As expected, the con®guration of the allyltin derivative (ca. 85:15 trans:cis) did not depend on
the con®guration of the starting allylic alcohol (since the xanthate±thiocarbonate rearrangement:
90!10 was not selective); however, treatment of the organometallic derivative with zinc chloride
exclusively furnished the trans-diene 12 in good yield.
Similarly, isomerically pure trans-diene 13 (d-xylo-con®gurated)8 was prepared from allyltin
derivative 15, which was in turn prepared from the known 3,5-di-O-benzyl-1,2-O-isopropylidene-
d-glucofuranose.9
2.2. Synthesis of the open-chain dienes from furanose derivatives
Application of the methodology presented in Scheme 1 to derivatives of furanoses should result
in similar transformations and provide dienes shorter by one carbon atom as compared to 2.
Conversion of 3-O-benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl-oct-6-ene-a-d-ribo-
1,4-furanose3 17 and its d-xylo- analog 24 into such valuable synthons is presented in Scheme 2.
Scheme 2. (i) ZnCl2, CH2Cl2, rt; (ii) Et3N, C6H6, MeOH, H2O; (iii) Ph3PˆCHCO2Me; (iv) NaBH4; (v) NaIO4
Treatment of 17 with zinc chloride a€orded hemiacetal 18; this product was relatively stable
and its conversion into hydroxyaldehyde 19 was achieved by mild basic hydrolysis. Aldehyde 19
y
Con®guration of the double bond in such a,b-unsaturated esters is not important for the stereochemical outcome of the
process leading to sugar allyltins. As we proved earlier (Ref. 3) the trans/cis mixture of the latter (with the sameÐꢁ6:1Ð
proportion of the trans:cis-isomers) is obtained regardless of the geometry of the double bond in the a,b-unsaturated ester.

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S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
may serve as starting material for the preparation of a variety of di€erently substituted chiral
dienes with the E-con®guration of the internal double bond (assigned from the coupling constant
J4,5 ꢁ14.5 Hz, observed on the H-5 resonance at ꢀ ca. 5.6 ppm). Reduction of the carbonyl group
in 19 with sodium borohydride gave diol 20, whilst the Wittig reaction with a stabilized ylide
a€orded triene 21. Periodic cleavage of diol 20 followed by reduction of resulting aldehyde with
NaBH4 provided alcohol 23 with only one stereogenic center.
A similar reaction sequence performed on the d-xylo-organometallic analog 24, prepared from
the corresponding allylic alcohol 2310 according to the methodology shown in Scheme 1, furnished
dienes 25±29 in good yields. The con®guration at the stereogenic center in 29 was, of course,
opposite to that in 22; thus, both enantiomers of this compound are available.
The methodology presented in Scheme 2 allows for facile preparation of a-hydroxyaldehydes
19 and 26 or the diols derived from themÐdiols 20 and 28. However, it is not very useful for the
simple preparation of fully protected dienoaldehydes, since the protection of the free hydroxy
group in a-hydroxyaldehydes is troublesome. Application of other (fully protected) sugar stannanes
may solve this problem (Scheme 3).
Scheme 3. (i) Swern oxidation; (ii) Ph3PˆCHCO2Me, CH2Cl2; (iii) (1) DIBAL-H; (2) NaH, THF, CS2, then MeI; (3)
toluene, 110ꢀC, 2 h; (4) Bu3SnH, AIBN, toluene, re¯ux; (iv) ZnCl2; (v) NaBH4
Methyl 2,3-di-O-benzyl-b-d-ribofuranoside11 30 was converted into unsaturated ester 31 as a ca.
4:1 mixture of E:Z-isomers and then into allyltin derivative 32 according to a method shown in
Scheme 2. Treatment of the latter with a Lewis acid induced a rearrangement with elimination of tri-n-
butyltin moiety and formation of the aldehyde 34, which was characterized further as alcohol 35.
3. Conclusion
The synthesis of di€erently substituted chiral, highly oxygenated dienes was realized by a mild
Lewis acid induced, controlled decomposition of sugar allyltins. This procedure gives mono-
substituted dienes with the trans-con®guration of the internal double bond exclusively. The con-
venient synthesis of unsaturated a-hydroxyaldehydes can also be realized by this methodology.
4. Experimental
4.1. General
NMR spectra were recorded with a Varian Gemini 200 spectrometer for solutions in CDCl3
(internal Me4Si). Mass spectra [LSIMS (m-nitrobenzyl alcohol was used as a matrix to which

S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
2001
sodium acetate was added) or EI] were recorded with an AMD-604 (AMD Intectra GmbH,
Germany) mass spectrometer. Speci®c rotations were measured with a JASCO DIP Digital
Polarimeter in chloroform solution (c ꢁ1) at room temperature. Column chromatography was
performed on silica gel (Merck, 70±230 mesh). Organic solutions were dried over anhydrous
magnesium or sodium sulfate.
4.2. Preparation of sugar allyltin derivatives
The sugar allyltin derivatives were prepared from the corresponding alcohols 5, 14, and 30
according to our previously published methods3 involving (cf. Scheme 1):
(i) oxidation of a sugar alcohol to an aldehyde;
(ii) reaction with the stabilized Wittig reagent (to a,b-unsaturated ester);
(iii) reduction of the ester function with DIBAL-H;
(iv) formation of a xanthate;
(v) its thermal rearrangement into thiocarbonate;
(vi) reaction with tri-n-butyltin hydride under radical conditions.
The procedure for the preparation of 11 is representative.
4.2.1. Methyl 2,3,5-tri-O-benzyl-6,7,8-trideoxy-8-tributylstannyl-ꢁ-d-galacto-oct-6-eno-1,4-furanoside
11
To a solution of the Swern reagent12 (prepared from 1 mL of oxalyl chloride and 3 mL of
DMSO in 30 mL of CH2Cl2) a solution of alcohol 57 (2.3 g, 5 mmol) in CH2Cl2 (15 mL) was
added at ^78ꢀC, and the mixture was stirred for 30 min at this temperature. Triethylamine (4 mL)
was added, the mixture was stirred at ^78ꢀC for another 30 min and partitioned between ether
(100 mL) and water (30 mL). The organic layer was separated, washed with water, dried and
concentrated, and the crude aldehyde 6 was dissolved in benzene (50 mL) containing
Ph3PˆCHCO2Me (2.34 g, 7 mmol). After 16 h at room temperature, the solvent was evaporated
in vacuum and the product ester 7 (trans:cis=2.5:1) was isolated by column chromatography
(hexane:ethyl acetate, 6:1!3:1); yield 82%.
1
trans-7: H NMR ꢀ: 6.94 (dd, J5,6=5.7, J6,7=15.8, H-6), 6.09 (d, H-7), 4.95 (J1,2=ꢁ0, H-1),
3.69 (CO2CH3), 3.35 (OCH3); 13C NMR ꢀ: 166.2 (CˆO), 144.4 and 123.1 (C-6,7), 107.1 (C-1),
87.7, 82.7, 82.6 and 76.7 (C-2,3,4,5), 72.1, 71.7 and 71.6 (3ÂCH2Ph), 54.9 and 51.6 (OCH3 and
CO2CH3); HRMS m/z: 541.2202 [C31H34O7Na (M+Na+) requires 541.2202].
1
cis-7: H NMR ꢀ: 6.35 (dd, J5,6=8.8, J6,7=11.7, H-6), 5.94 (dd, J5,7=0.87, H-7), 4.98 (d,
J1,2=1.1, H-1), 3.67 (CO2CH3), 3.33 (OCH3); 13C NMR ꢀ: 165.9 (CˆO), 146.9 and 121.9 (C-6,7),
107.2 (C-1), 87.9, 83.5 and 82.5 (C-2,3,4), 73.2, 72.0 and ꢁ71 (3ÂCH2Ph), 54.9 and 51.4 (OCH3
and CO2CH3).
To a cooled ^78ꢀC solution of 7 (5 g, 9.7 mmol) in dry methylene chloride a 1 M solution of
DIBAL-H in hexane (20 mL, 20 mmol) was added and the mixture was stirred for 2 h at ^78ꢀC.
The excess of hydride was decomposed by addition of ethyl acetate (2 mL) and, after warming to
room temperature, water (10 mL). Insoluble material was ®ltered o€ by suction, the ®ltrate was
dried, concentrated, and the productÐalcohol 8Ðwas isolated by column chromatography
(hexane:ethyl acetate, 4:1!2:1); yield 86%. HRMS m/z: 513.2252 [C31H34O7Na (M+Na+)
requires 513.2253].

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S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
(Caution: The next sequence of reactions must be performed in a well-ventilated fume hood). To a
solution of alcohol 8 (4.02 g, 8.2 mmol) in dry THF (30 mL) sodium hydride (ca. 60% suspension in
mineral oil, 0.5 g) was added followed by a catalytic amount of imidazole (ca. 50 mg). The mix-
ture was stirred at room temperature under an argon atmosphere for 1 h. Carbon disul®de (neat,
1 mL) was added and the mixture was stirred for another 30 min. MeI (1.5 mL) was then added,
the mixture was stirred for 2 h at room temperature, and partitioned between ether (50 mL) and
brine (20 mL). The organic layer was separated, washed with water, dried, and concentrated.
A solution of crude xanthate 9 in dry toluene was purged with argon and heated under re¯ux until
TLC (hexane:ethyl acetate, 5:1) indicated disappearance of the starting material and formation of
a new slightly less polar product thiocarbonate 10 (2±3 h, two stereoisomers of very similar polarity
were seen by TLC). Tri-n-butyltin hydride (2.9 mL, 11 mmol) in toluene (5 mL) was added dropwise
over 5 min (caution: reaction is very exothermic), and heating was continued until TLC (hexane:ethyl
acetate, 6:1) indicated disappearance of starting material and formation of a new less polar
product (ca. 30 min). The solvent was evaporated under vacuum and the product was puri®ed by
column chromatography (hexane:diethyl ether, 20:1!9:1) to a€ord 11 as colorless syrup, yield 53%.
Compound 11 (pure trans-isomer). 1H NMR ꢀ: 5.82 (ddd, J6,7=15.2, J7,8a=8.6, J7,8b=6.7, H-7),
5.34 (dd, J5,6=8.8, H-6), 4.96 (d, J1,2=ꢁ1, H-1), 3.79 (dd, J4.5=3, H-4), 3.35 (OCH3); 13C NMR
ꢀ: 136.0 and 121.6 (C-6,7), 107.0 (C-1), 88.3, 84.0, 83.3 and 78.7 (C-2,3,4,5), 72.2, 71.7 and 69.4
(3ÂCH2Ph), 54.7 (OCH3), 29.8, 27.3 and 9.9 [3ÂSn(CH2)3CH3], 14.5 (C-8), 13.7 [Sn(CH2)CH3];
HRMS m/z: 707.2743 [C38H51O1520Sn (M^57) requires 707.2759].
4.2.2. 3,5-Di-O-benzyl-1,2-O-isopropylidene-6,7,8-trideoxy-8-tributylstannyl-ꢂ-d-gluco-oct-6-eno-1,4-
furanose 15
This compound was prepared as a 9:1 trans:cis mixture from known 3,5-di-O-benzyl-1,2-O-
isopropylidene-a-d-glucofuranose9 according to the above procedure. Overall yield: 45%. MS-EI
m/z: [643, M^57]; 1H NMR for trans-15 ꢀ: 5.98 (ddd, J6,7=15.2, J7,8a=8.0, J7,8b=5.9, H-7), 5.89
(d, J1,2=3.7, H-1), 5.29 (m, H-6), 1.83 (m, H-8a,b), 1.47 and 1.29 [C(CH3)2]; 13C NMR ꢀ: 136.5
and 123.0 (C-6,7), 111.4 [C(CH3)2], 104.9 (H-1), 82.2, 81.9, 81.7 and 77.6 (C-2,3,4,5), 72.2 and
69.5 (2ÂCH2Ph), 29.1, 27.3 and 13.7 [Sn(CH2)3CH3], 26.7 and 26.3 [C(CH3)2], 14.6 (C-8), 9.2
[Sn(CH2)3CH3].
4.2.3. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl-ꢂ-d-xylo-hept-5-eno-1,4-
furanose 24
This compound was prepared as a ca. 4:1 mixture of trans:cis-isomers from known 3-O-benzyl-
1,2-O-isopropylidene-5,6-di-deoxy-a-d-xylo-hept-5(E/Z)-eno-1,4-furanose according to the pro-
cedure described in Section 4.2.1.
HRMS m/z: 523.1880 [C25H39O1420Sn (M^57) requires 523.1870]; H NMR data for the trans-
1
isomer ꢀ: 5.99 (m, H-6), 5.85 (d, J1,2=4.0, H-1), 5.45 (m, H-5), 3.71 (J2,3=ꢁ0, J3,4=2.9, H-3),
1.50 and 1.30 [C(CH3)2]; 13C NMR ꢀ: 136.9 and 118.2 (C-5,6), 111.0 [C(CH3)2], 104.4 (C-1), 83.9,
82.8 and 82.1 (C-2,3,4), 72.1 (CH2Ph), 29.1, 27.3 and 13.7 [3ÂSn(CH2)3CH3], 26.7 and 26.1,
[C(CH3)2], 14.8 (C-7), 9.3 [Sn(CH2)3CH3].
4.2.4. Methyl 2,3-di-O-benzyl-5,6,7-trideoxy-7-tributylstannyl-ꢁ-d-ribo-hept-5-eno-1,4-furanoside
32
This compound was prepared from known11 alcohol 30, via unsaturated ester 31 {ca. 4:1
trans:cis mixture. HRMS m/z: 421.1625 [C23H26O6Na (M+Na+) requires 421.1627]; data for the

S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
2003
main trans-isomer: 1H NMR ꢀ: 6.94 (dd, J4,5=5.5, J5,6=15.8, H-5), 6.10 (dd, J4,6=1.5, H-6), 4.92
(J1,2=ꢁ0, H-1), 3.74 (CO2CH3), 3.36 (OCH3); 13C NMR ꢀ: 146.6 and 121.2 (CˆO), 106.4 (C-1),
81.8, 79.8 and 79.5 (C-2,3,4), 72.8 and 72.4 (2ÂCH2Ph), 55.6 and 51.6 (OCH3 and CO2CH3)}
according to the procedure described in Section 4.2.1.
1
Compound 32 (only trans). H NMR ꢀ: 5.92 (ddd, J5,6=14.9, J6,7a=8.8, J6,7b=8.5, H-6), 5.21
(dd, J4,5=8.3, H-5), 4.86 (J1,2=ꢁ0, H-1), 3.34 (OCH3); 13C NMR ꢀ: 135.2 and 124.4 (C-5,6),
105.6 (C-1), 82.8, 82.3 and 80.1 (C-2,3,4), 72.5 and 72.2 (2ÂCH2Ph), 54.9 (OCH3), 29.1, 27.3 and
9.2 [Sn(CH2)3CH3], 14.6 (C-7), 13.8 [Sn(CH2)3CH3]; HRMS m/z: 667.2789 [C34H52O4Na120Sn
(M+Na+) requires 667.2785].
4.3. Reaction of sugar allyltin derivatives with Lewis acids
The corresponding allyltin derivative (11, 15, 17, 24 or 32; 3 mmol each) was dissolved in
anhydrous methylene chloride (30 mL). A 2.0 M solution of ZnCl2 etherate in methylene chloride
(3 mL, 6 mmol) was added, the mixture was stirred at room temperature for 20 min, and partitioned
between ether (50 mL) and brine (30 mL). The organic layer was separated, washed with water,
dried and concentrated and the products were isolated by column chromatography (hexane:diethyl
ether, 7:1). Dienes 18 and 25 were characterized as acetates.
4.3.1. Methyl 2,3-di-O-benzyl-5,6,7,8-tetradeoxy-ꢁ-l-arabino-oct-5(E),7-dieno-1,4-furanoside 12
1H NMR ꢀ: 6.33 (m, H-6,7), 5.72 (dd, J4,5=7.8, J5,6=14.1, H-5), 5.19 (m, both H-8), 4.91 (d,
J1,2=1.3, H-1), 4.44 (m, J3,4=7.1, H-4), 4.00 (dd, J2,3=3.5, H-2), 3.78 (dd, H-3), 3.37 (OCH3);
13C NMR ꢀ: 136.0, 133.8 and 130.8 (C-5,6,7), 118.4 (C-8), 88.6, 87.5 and 81.3 (C-2,3,4), 72.3 and
72.0 (2ÂCH2Ph), 54.8 (OCH3); HRMS m/z: 389.1752 [C23H26O4Na (M+Na+) requires 389.1729].
4.3.2. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7,8-tetradeoxy-ꢂ-d-xylo-oct-5(E),7-dieno-1,4-furanose8
13
When this compound was prepared by controlled decomposition of allyltin 15 only the trans-
isomer was detected in the NMR spectra.
1H NMR ꢀ: 6.36 (m, H-6,7), 5.95 (d, J1,2=3.8, H-1), 5.85 (dd, J4,5=7.5, J5,6=14.8, H-5), 5.20
(m, both H-8), 3.85 (dd, J3,4=3.1, H-3), 1.50 and 1.31 [C(CH3)2]; 13C NMR ꢀ: 136.1, 134.6, 127.1
(C-5,6,7), 118.2 (C-8), 111.4 [C(CH3)2], 104.7 (C-1), 83.4, 82.9, 80.8 (C-2,3,4), 72.0 (CH2Ph), 26.7,
26.1 [C(CH3)2].
When this product was obtained according to Narkunan and Nagarajan8 (see also Scheme 1)
additional signals, that could be connected with the cis-isomer, were seen in the 13C NMR spec-
1
trum at ꢀ: 133.0, 131.7, 125.0 (C-5,6,7), 119.8 (C-8), and 112.1 [C(CH3)2]. Also, in the H NMR
spectrum the H-3 resonance split into two signals at ꢀ: 3.89 (the minor cis-isomer) and 3.85
(the main trans-isomer). Integration of these signals allowed us to estimate the trans:cis ratio at
9:1.
4.3.3. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-erythro-heptose
18-Ac
1H NMR ꢀ: 6.36 (m, H-5,6), 6.22 (d, J1,2=2.3, H-1), 5.65 (dd, J3,4=7.7, J4,5=14.5, H-4), 5.21
(m, H-7), 4.23 (dd, J2,3=6.2, H-2), 3.87 (dd, H-3), 2.07 (COCH3), 1.47 and 1.46 [C(CH3)2]; 13C
NMR ꢀ: 170.1 (CˆO), 135.9, 135.8 and 129.0 (C-4,5,6), 118.7 (C-7), 112.9 [C(CH3)2], 96.6 (C-1),
83.6 and 78.8 (C-2,3), 70.5 (CH2Ph), 27.2 and 26.7 [C(CH3)2], 21.2 (COCH3).

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S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
4.3.4. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-threo-heptose
25-Ac
1H NMR ꢀ: 6.34 (m, H-5,6), 6.17 (d, J1,2=2.3, H-1), 5.63 (dd, J3,4=8.2, J4,5=14.6, H-4), 5.20
(m, both H-7), 4.30 (dd, J2,3=5.5, H-2), 3.95 (dd, H-3), 2.06 (COCH3), 1.48 and 1.44 [C(CH3)2];
13C NMR ꢀ: 170.2 (CˆO), 136.2, 135.5 and 128.7 (C-4,5,6), 118.9 (C-7), 113.1 [C(CH3)2], 96.4
(C-1), 83.8 and 78.3 (C-2,3), 70.2 (CH2Ph), 27.0 and 26.9 [C(CH3)2], 21.2 (COCH3); HRMS m/z:
355.1521 [C19H24O5Na (M+Na+) requires 355.1521].
4.4. Basic hydrolysis of dioxolanes 18 and 25
To a solution of 18 or 25 (3 mmol) in benzene (30 mL), triethylamine (1 mL), methanol (1 mL)
and water (1 mL) were added and the mixture was stirred at room temperature for 3 h. Toluene
(20 mL) was added, and the solution was concentrated to ca. half volume, dried and concentrated
to give in almost quantitative yield 2(R)-hydroxy-3(R)-benzyloxy-hepta-4(E),6-dienal 19 and 2(R)-
hydroxy-3(S)-benzyloxy-hepta-4(E),6-dienal 26. These hydroxyaldehydes were rather unstable
and should be prepared directly before use in the next step.
4.5. Reaction of hydroxyaldehydes with the stabilized Wittig reagent
Freshly prepared aldehyde (19 or 26; 1 mmol) was dissolved in dry benzene (10 mL) to
which Ph3PˆCH±CO2Me (0.5 g, 1.5 mmol) was added. The mixture was stirred for 3 h at room
temperature, concentrated, and the product was isolated by column chromatography (hexane:ethyl
acetate, 6:1).
4.5.1. Methyl 4(R)-hydroxy-5(R)-benzyloxy-nona-2(E),6(E),8-trienoate 21
[ꢂ]D ^87.7. 1H NMR ꢀ: 6.95 (dd, J2,3=15.8, J3,4=4.6, H-3), 6.33 (m, H-7,8), 6.11 (dd, J2,4=1.7,
H-2), 5.62 (dd, J5,6=8.1, J6,7=14.5, H-6), 5.22 (m, both H-9), 4.36 (H-4), 3.93 (dd, J4,5=4.4,
H-5), 3.72 (CO2CH3); 13C NMR ꢀ: 166.7 (CˆO), 145.7 and 121.6 (C-2,3), 136.2, 135.7 and 128.7
(C-6,7,8), 118.9 (C-9), 81.6 (C-5), 72.9 (C-4), 70.4 (CH2Ph), 51.5 (CO2CH3); HRMS m/z:
311.1280 [C17H20O4Na (M+Na+) requires 311.1259].
4.5.2. Methyl 4(R)-hydroxy-5(S)-benzyloxy-nona-2(E),6(E),8-trienoate 27
1
[ꢂ]D +116.0. H NMR ꢀ: 6.89 (dd, J2,3=15.6, J3,4=4.2, H-3), 6.36 (m, H-7,8), 6.16 (dd,
J2,4=1.9, H-2), 5.61 (dd, J5,6=8.4, J6,7=14.3, H-6), 5.24 (m, both H-9), 4.27 (m, H-4), 3.73 (H-5,
CO2CH3); 13C NMR ꢀ: 166.7 (CˆO), 145.6 and 121.6 (C-2,3), 136.6, 135.6 and 128.8 (C-6,7,8),
119.3 (C-9), 82.2 (C-5), 73.1 (C-4), 70.4 (CH2Ph), 51.6 (CO2CH3); HRMS m/z: 311.1289
[C17H20O4Na (M+Na+) requires 311.1259].
4.6. Reduction of hydroxyaldehydes 19, 26 and alkoxyaldehyde 34
Freshly prepared aldehyde 19 or 26 (1 mmol; obtained by hydrolysis of the corresponding
dioxolanes, 18 and 25) or 34 (obtained by the controlled decomposition of 1 mmol of allyltin 32
according to Section 4.3) was dissolved in a THF:methanol mixture (1:1 v/v, 20 mL), to which
sodium borohydride (0.1 g) was added. The mixture was stirred for 1 h, concentrated, then the
product was extracted with ether, acetylated under standard conditions and puri®ed by column
chromatography (hexane:ethyl acetate, 2:1).

S. Jarosz et al. / Tetrahedron: Asymmetry 11 (2000) 1997±2006
2005
4.6.1. 1,2(R)-Di-acetoxy-3(R)-benzyloxy-hepta-4(E),6-diene 20-Ac
[ꢂ]D ^88.9. 1H NMR ꢀ: 6.33 (m, H-5,6), 5.60 (dd, J3,4=8.1, J4,5=14.3, H-4), 5.20 (m, H-2, both
H-7), 3.96 (dd, J2,3=6.2, H-3), 2.01 and 1.99 (2ÂCOCH3); 13C NMR ꢀ: 170.5 and 170.0
(2ÂCˆO), 135.7, 135.6 and 129.3 (C-4,5,6), 118.7 (C-7), 77.6 and 72.4 (C-2,3), 70.3 (CH2Ph), 62.4
(C-1), 20.8 and 20.7 (2ÂCOCH3); HRMS m/z: 341.1362 [C18H22O5Na (M+Na+) requires
341.1365].
4.6.2. 1,2(R)-Di-acetoxy-3(S)-benzyloxy-hepta-4(E),6-diene 28-Ac
[ꢂ]D +26.6. 1H NMR ꢀ: 6.34 (m, H-5,6), 5.59 (dd, J3,4=7.8, J4,5=14.5, H-4), 5.22 (m, H-2, both
H-7), 4.31 and 4.10 (2Âdd, J1a,1b=11.8, J1a,2=3.7, J1b,2=7.0, both H-1), 4.01 (dd, J2,3=5.3,
H-3), 2.08 and 1.99 (2ÂCOCH3); 13C NMR ꢀ: 170.5 and 170.2 (2ÂCˆO), 135.7, 135.5 and ꢁ128
(C-4,5,6), 118.9 (C-7), 77.2 and 72.5 (C-2,3), 70.4 (CH2Ph), 62.8 (C-1), 20.9 and 20.7
(2ÂCOCH3); HRMS m/z: 341.1350 [C18H22O5Na (M+Na+) requires 341.1365].
4.6.3. 1-Acetoxy-2(R),3(S)-di-benzyloxy-hepta-4(E),6-diene 35-Ac
1H NMR ꢀ: 6.35 (m, H-5,6), 5.68 (dd, J3,4=8.1, J4,5=14.5, H-4), 5.21 (m, both H-7), 4.32 (dd,
J1a,1b=11.8, J1a,2=3.7, H-1a), 4.19 (dd, J1b,2=5.7, H-1b), 3.95 (dd, J2,3=5.7, H-3), 3.68 (m,
H-2), 1.98 (COCH3); 13C NMR ꢀ: 170.8 (CˆO), 136.0, 135.2 and 130.6 (C-4,5,6), 118.1 (C-7),
79.0 and 78.8 (C-2,3), 72.8 and 70.4 (2ÂCH2Ph), 63.4 (C-1), 20.9 (COCH3); HRMS m/z: 389.1725
[C23H26O4Na (M+Na+) requires 389.1729].
4.7. Synthesis of dienes 22 and 29
Diol 20 or 28 (1 mmol) was dissolved in ether (20 mL) and added to a solution of sodium
periodate (0.7 g) in water (10 mL). The heterogeneous mixture was stirred for 30 min, the organic
layer was separated, dried and concentrated, and the crude aldehyde was reduced with sodium
borohydride as described in Section 4.6. For better characterization, products alcohols 22 and 29
were acetylated and these derivatives were puri®ed by column chromatography (hexane:ethyl
acetate, 4:1)
4.7.1. 1-Acetoxy-2(R)-benzyloxy-hexa-3(E),5-diene 22-Ac
1
[ꢂ]D ^87.9. H NMR ꢀ: 6.35 (m, H-4,5), 5.61 (dd, J2,3=6.8, J3,4=14.3, H-3), 5.19 (m, both H-
6), 4.11 (m, H-2, both H-1), 2.05 (COCH3); 13C NMR ꢀ: 170.8 (CˆO), 135.8, 134.8 and 129.6 (C-
3,4,4), 118.6 (C-6), 76.9 (C-2), 70.4 (CH2Ph), 66.2 (C-1), 20.8 (COCH3); HRMS m/z: 269.1165
[C15H18O3Na (M+Na+) requires 269.1154].
4.7.2. 1-Acetoxy-2(S)-benzyloxy-hexa-3(E),5-diene 29-Ac (=ent-22-Ac)
[ꢂ]D +85.5. HRMS m/z: 269.1153 [C15H18O3Na (M+Na+) requires 269.1154]. The NMR spectra
of this compound were identical in all respects with the spectra of 22-Ac.
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